The role of the side chain in determining relative delta- and kappa-affinity in C5'-substituted analogues of naltrindole

J Med Chem. 2003 Jan 16;46(2):314-7. doi: 10.1021/jm020997b.

Abstract

The role of the side chain in 5'-substituted analogues of naltrindole has been further explored with the synthesis of series of amides, amidines, and ureas. Amidines (8, 13) had greatest selectivity for the kappa receptor, as predicted from consideration of the message-address concept. It was also found that an appropriately located carbonyl group, in ureas (10) and amides (7), led to retention of affinity and antagonist potency at the delta receptor.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amides / chemical synthesis
  • Amides / chemistry
  • Amides / pharmacology
  • Amidines / chemical synthesis
  • Amidines / chemistry
  • Amidines / pharmacology
  • Animals
  • CHO Cells
  • Cricetinae
  • Humans
  • Naltrexone / analogs & derivatives*
  • Naltrexone / chemical synthesis*
  • Naltrexone / chemistry
  • Naltrexone / pharmacology
  • Narcotic Antagonists / chemical synthesis*
  • Narcotic Antagonists / chemistry
  • Narcotic Antagonists / pharmacology
  • Radioligand Assay
  • Receptors, Opioid, delta / antagonists & inhibitors*
  • Receptors, Opioid, delta / metabolism
  • Receptors, Opioid, kappa / antagonists & inhibitors*
  • Receptors, Opioid, kappa / metabolism
  • Urea / analogs & derivatives
  • Urea / chemical synthesis
  • Urea / chemistry
  • Urea / pharmacology

Substances

  • Amides
  • Amidines
  • Narcotic Antagonists
  • Receptors, Opioid, delta
  • Receptors, Opioid, kappa
  • Naltrexone
  • Urea
  • naltrindole